[Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium].

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

[Research progress of continuous manufacturing and process knowledge system of traditional Chinese medicine].

In the past few years, continuous manufacturing(CM) has been put forward by the FDA. Pharmaceutical enterprises are encouraged to promote the implementation of CM, which has become a hot research direction of pharmaceutical technology. In February 2019, the FDA issued a draft guideline for the implementation of CM, which greatly promoted the development of CM and provided reference for continuous manufacturing of traditional Chinese medicine(TCM). The production process of TCM is a complex system. With the innovation of production equipment and the promotion of automation and informatization of TCM production, the exis-ting policies, regulations and traditional production control capacity are difficult to meet the market demand for high-quality TCM pro-ducts. In this paper, we reviewed the new technologies and methods of quality control in accordance with the characteristics of TCM production by referring to modern manufacturing technology, information technology and quality control technology. Based on the "QbD" theory and "PAT" technology, process knowledge system(PKS), an advanced control strategy, was proposed to provide a reference for the implementation of CM in TCM production.

Capture and Release of Singlet Oxygen in Coordination-Driven Self-Assembled Organoplatinum(II) Metallacycles.

Singlet oxygen (1O2), as an important active reagent, has found wide applications in photodynamic therapy (PDT), synthetic chemistry, and materials science. Organic conjugated aromatics serving as hosts to capture and release singlet oxygen have been systematically investigated over the last decades. Herein, we present a [6 + 6] organoplatinum(II) metallacycle by using ∼180° dipyridylanthracene donor and ∼120° Pt(II) acceptor as the building blocks, which enables the capture and release of singlet oxygen with relatively high photooxygenation and thermolysis rate constants. The photooxygenation of the metallacycle to the corresponding endoperoxide was performed by sensitized irradiation, and the resulting endoperoxide is stable at room temperature and can be stored under ambient condition over months. Upon simple heating of the neat endoperoxide under inert atmosphere at 120 °C for 4 h, the resulting endoperoxide can be reconverted to the corresponding parent form and singlet oxygen. The photooxygenation and thermolysis products were characterized by NMR spectroscopy and electrospray ionization time-of-flight mass spectrometric analysis. Density functional theory calculations were conducted in order to reveal the frontier molecular orbital interactions and reactivity. This work provides a new material platform for singlet oxygen related promising applications.

Metal-Organic Pt(II) Hexagonal-Prism Macrocycles and Their Photophysical Properties.

In this work, we present the formation of two open-ended hexagonal-prism tubular macrocycles by the [6 + 12] self-assembly of the symmetric ∼120° organic ligand donor with ∼90° Pt(II) acceptor in a 1:2 ratio. The assembled structures were characterized by multinuclear NMR (1H NMR, 31P{1H} NMR, and 1H-1H COSY NMR), electrospray ionization mass spectrometry (ESI-TOF-MS), traveling wave ion mobility-mass spectrometry (TWIM-MS), and transmission electron microscopy. Molecular modeling was further conducted to get insight into their structured characteristics. We also examined their photophysical properties.

Transition from a Metal-Localized Mixed-Valence Compound to a Fully Delocalized and Bridge-Biased Electrophore in a Ruthenium-Amine-Ruthenium Tricenter System.

A series of cyclometalated diruthenium complexes with a redox-active amine bridge were synthesized. Depending on the terminal ligands of the ruthenium components and the substituent on the amine unit, the one-electron-oxidized state can be either in the form of a weakly or strongly coupled mixed-valence diruthenium complex, a fully charge-delocalized three-center system, or a bridge-biased electrophore. This transition among different electronic forms was supported by electrochemistry, near-infrared absorption, electron paramagnetic resonance, and density functional theory analysis.

Construction and Activity Evaluation of Novel Bifunctional Inhibitors and a COF Carrier Based on a Fungal Infection Microenvironment.

Faced with increasingly serious fungal infections and drug resistance issues, three different series of novel dual-target (programmed death ligand 1/14 α-demethylase) compounds were constructed through the fragment combination pathway in the study. Their chemical structures were synthesized, characterized, and evaluated. Among them, preferred compounds 10c-1, 17b-1, and 18b-2 could efficiently exert their antifungal and antidrug-resistant fungal ability through blocking ergosterol biosynthesis, inducing the upregulation of reactive oxygen species level, and triggering apoptosis. Especially, compound 18b-2 exhibited the synergistic function of fungal inhibition and immune activation. Moreover, the covalent organic framework carrier was also generated based on the acidic microenvironment of fungal infection to improve the bioavailability and targeting of preferred compounds; this finally accelerated the body's recovery rate.

Ciclopirox platinum(IV) conjugates suppress tumors by promoting mitophagy and provoking immune responses.

Mitophagy is an important target for antitumor drugs development. A series of ciclopirox (CPX) platinum(IV) hybrids targeting PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitophagy were designed and prepared as antitumor agents. The dual CPX platinum(IV) complex with cisplatin core was screened out as a candidate, which displayed promising antitumor activities both in vitro and in vivo. Mechanistically, it caused serious DNA damage in tumor cells. Then, remarkable mitochondrial damage was induced accompanied by the mitochondrial membrane depolarization and reactive oxygen species generation, which further promoted apoptosis through the Bcl-2/Bax/Caspase3 pathway. Furthermore, mitophagy was ignited via the PINK1/Parkin/P62/LC3 axis, and exhibited positive influence on promoting the apoptosis of tumor cells. The antitumor immunity was boosted by the block of immune check point programmed cell death ligand-1 (PD-L1), which further increased the density of T cells in tumors. Subsequently, the metastasis of tumor cells was inhibited by inhibiting angiogenesis in tumors.

A hydroxychloroquine platinum(IV) conjugate displaying potent antimetastatic activities by suppressing autophagy to improve the tumor microenvironment.

Protective autophagy is a promising target for antitumor drug exploration. A hydroxychloroquine (HCQ) platinum(IV) complex with autophagy suppressing potency was developed, which displayed potent antitumor activities with a TGI rate of 44.2% against 4T1 tumors in vivo and exhibited a rather lower toxicity than cisplatin. Notably, it exhibited satisfactory antimetastatic activities toward lung pulmonary metastasis models with an inhibition rate of 49.6% and was obviously more potent than CDDP, which has an inhibition rate of 21.6%. Mechanism detection revealed that it caused serious DNA damage and upregulated the expression of γ-H2AX and p53. More importantly, the incorporation of an autophagy inhibitor HCQ endowed the platinum(IV) complex with potent autophagy impairing properties by perturbing the lysosomal function in tumor cells, which promoted apoptosis synergistically with DNA injury. Then, the impaired autophagy further led to the suppression of hypoxia and inflammation in the tumor microenvironment by downregulating ERK1/2, HIF-1α, iNOS, caspase1 and COX-2. Adaptive immune response was improved by inhibiting the immune checkpoint PD-L1 and further increasing CD4+ and CD8+ T cells in tumors. Then, tumor metastasis was effectively inhibited by restraining angiogenesis through inhibiting VEGFA, MMP-9, and CD34.

Flexible and efficient eletrokinetic stacking of DNA and proteins at an HF etched porous junction on a fused silica capillary.

Better understanding of the mechanism is important for exploring the potentials of a preconcentration method. In this work, we show for the first time that the HF etched porous junction on a fused silica capillary behaves not only as a filter but also as an integrated nanofluidic interface. This junction exhibits an obvious ion concentration polarization (CP) effect, with which highly efficient electrokinetic stacking (ES) inside the capillary can be achieved without molecular size or charge type limitation. Two major types of CP based ES were proposed, and an autostop etching principle was presented for avoiding overetching. The ES can be performed in a broad range of pH and buffer concentration. Over a billion times of concentration was demonstrated by a fluorescein probe with laser induced fluorescent (LIF) detection. ES of fluorescently labeled and native DNA and protein were characterized by charge-coupled device (CCD) imaging and online capillary gel electrophoresis (CGE) with ultraviolet (UV) absorption detections, respectively. With this junction, highly efficient ES can be performed easily by voltage manipulation without any mechanical operation. We may foresee that the performance of capillary-based conventional and chip electrophoresis could be greatly enhanced with this junction in the analysis of low abundance biomolecules.

Diethyl 4-meth-oxyoxalyl-3,5-diphenyl-pyrrolidine-2,2-dicarboxyl-ate.

In the title compound, C(25)H(27)NO(7), the pyrrolidine ring exhibits an envelope conformation and the benzene rings form a dihedral angle of 33.47 (11)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers. Weak C-H⋯O inter-actions link the dimers into layers parallel to the bc plane.

Evaluating the impact of personalized rehabilitation nursing intervention on postoperative recovery of respiratory function among thoracic surgery intensive care unit patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Exercise tolerance and lung function can be improved by pulmonary rehabilitation. As a result, it may lower thoracic surgery intensive care unit (ICU) patients' postoperative problems and death. Enhanced recovery after surgery has advanced significantly in the perioperative care of thoracic surgery ICU patients in recent years, and it now plays an essential role in improving ICU patients' postoperative prognosis. Appropriate tailored rehabilitation nursing intervention is required to promote the postoperative recovery of respiratory function in thoracic surgery ICU patients. This study aims to look at the influence of tailored rehabilitation nurse intervention on postoperative respiratory function recovery in thoracic surgery ICU patients. METHODS: To find relevant papers, a comprehensive search of electronic databases will be conducted, including three English databases (PubMed, EMBASE, and the Cochrane Library) and two Chinese databases (Chinese National Knowledge Infrastructure and WanFang). Only research that has been published in either English or Chinese will be considered. The retrieval period will run from November 2021 to November 2021. We will look at randomized controlled trials (RCTs) studies that looked at the effect of a customized rehabilitation nursing intervention on the recovery of respiratory function in thoracic surgery ICU patients after surgery. Two writers will review the literature, retrieve study data, and assess the included studies' quality. Any disagreements will be settled via consensus. RevMan 5.3 will be used to do the meta-analysis. RESULTS: This research will offer high-quality data on the influence of customized rehabilitation nurse intervention on postoperative respiratory function recovery in thoracic surgery ICU patients. CONCLUSION: This study will look at whether a targeted rehabilitation nurse intervention might help thoracic surgery ICU patients recover their respiratory function more quickly after surgery. ETHICS AND DISSEMINATION: There will be no need for ethical approval. REGISTRATION NUMBER: December 12, 2021.osf.io/9rdu2/ (https://osf.io/9rdu2/).

Acupoint Massage Therapy Alters the Composition of Gut Microbiome in Functional Constipation Patients.

RESULTS: Results showed the overall structure of gut microbiome has no significant difference between experimental and control groups. In the genus level, the abundance of Pseudobutyrivibrio and Ruminiclostridium is higher in the experiment group than in the control, whereas that of Fusicatenibacter is less. The 16S KEGG function prediction suggested that Parkinson disease, retinol metabolism, and arachidonic acid metabolism could explain the biological function of different gut microbiome. Furthermore, cytokines in the serum showed a correlation with the abundance of Pseudobutyrivibrio in CFC. CONCLUSION: AMT could change the composition of gut microbiome which is associated with cytokines in CFC patients.

MicroRNA-197 controls ADAM10 expression to mediate MeCP2's role in the differentiation of neuronal progenitors.

Duplication of MECP2 (Methyl-CpG-binding protein 2) causes severe mental illness called MECP2 duplication syndrome (MDS), yet the underlying mechanism remains elusive. Here we show, in Tg(MECP2) transgenic mouse brain or cultured neural progenitor cells (NPCs), that elevated MeCP2 expression promotes NPC differentiation into neurons. Ectopic expression of MeCP2 inhibits ADAM10 and thus the NOTCH pathway during NPC differentiation. In human cells, this downregulation on ADAM10 was mediated by miRNA-197, which is upregulated by MeCP2. Surprisingly, miR-197 binds to the ADAM10 3'-UTR via its 3' side, not the canonical seed sequence on the 5' side. In mouse cells, a noncoding RNA Gm28836 is used to replace the function of miR-197 between MeCP2 and ADAM10. Similar to MeCP2, overexpressing miR-197 also promotes NPCs differentiation into neurons. Interestingly, three rare missense mutations (H371R, E394K, and G428S) in MECP2, which we identified in a Han Chinese autism spectrum disorders (ASD) cohort showed loss-of-function effects in NPC differentiation assay. These mutations cannot upregulate miR-197. Overexpressing miR-197 together with these MeCP2 mutations could rescue the downregulation on ADAM10. Not only the inhibitor of miR-197 could reverse the effect of overexpressed MeCP2 on NPCs differentiation, but also overexpression of miR-197 could reverse the NPCs differentiation defects caused by MECP2 mutations. Our results revealed that a regulatory axis involving MeCP2, miR-197, ADAM10, and NOTCH signaling is critical for NPC differentiation, which is affected by both MeCP2 duplication and mutation.

Making of a single solid-state nanopore on the wall of fused silica capillary.

A channel of nanometre size is an important platform for nanofluidic investigations. In this work, we show that a single solid nanopore can be generated by hydrogen fluoride etching of the outside wall of commercially available fused silica capillary. The geometry, size and the singleness were characterized by various means, including scanning electron microscope, electrolyte conductance measurement and a fluorescent microscope. The generation principle is also discussed. The nanopore thus generated features in low aspect ratio and exhibits typical nanofluidic effects such as ion concentration polarization, rectification and molecular translocation.

Multistate Redox Switching and Near-Infrared Electrochromism Based on a Star-Shaped Triruthenium Complex with a Triarylamine Core.

A star-shaped cyclometalated triruthenium complex 2(PF6)n (n = 3 and 4) with a triarylamine core was synthesized, which functions as a molecular switch with five well-separated redox states in both solution and film states. The single-crystal X-ray structure of 2(PF6)3 is presented. This complex displays four consecutive one-electron redox waves at +0.082, +0.31, +0.74, and +1.07 V vs Ag/AgCl. In each redox state, it shows significantly different NIR absorptions with λmax of 1590 nm for 24+, 1400 nm for 25+, 1060 nm for 26+, and 740 nm for 27+, respectively. Complex 24+ shows a single-line EPR signal at g = 2.060, while other redox states are all EPR inactive. The spin density distributions and NIR absorptions in different redox states were rationalized by DFT and TDDFT calculations. A vinyl-substituted triruthenium analogous 3(PF6)4 was prepared, which was successfully polymerized on ITO glass electrode surfaces by reductive electropolymerization. The obtained poly-3n+/ITO film was characterized by FTIR, AFM, and SEM analysis. It shows four well-defined redox couples and reversible multistate NIR electrochromism. In particular, a contrast ratio (ΔT%) up to 63% was achieved at the optic telecommunication wavelength (1550 nm).

The synthesis of 2- and 2,7-functionalized pyrene derivatives through Ru(II)-catalyzed C-H activation.

Through Ru(II)-catalyzed C-H bond activation, a methodology for the synthesis of 2- or 2,7-functionalized pyrene derivatives has been developed using the substrate 1-(pyrid-2-yl)pyrene or 1,6-di(pyrid-2-yl)pyrene.